Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001022358 | SCV001184087 | likely benign | Hereditary cancer-predisposing syndrome | 2021-01-27 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Invitae | RCV001050539 | SCV001214654 | uncertain significance | Tuberous sclerosis 2 | 2024-01-27 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 1454 of the TSC2 protein (p.Ser1454Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with This variant has been observed in individual(s) with Tuberous Sclerosis Complex. However, in that individual pathogenic allele[s] were also identified in TSC1, which suggests that c.4360A>G variant was not the primary cause of disease. (PMID: 22903760). ClinVar contains an entry for this variant (Variation ID: 49830). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TSC2 protein function with a negative predictive value of 95%. Experimental studies have shown that this missense change does not substantially affect TSC2 function (PMID: 22903760). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Genome- |
RCV001050539 | SCV002040824 | uncertain significance | Tuberous sclerosis 2 | 2021-11-07 | criteria provided, single submitter | clinical testing | |
| Tuberous sclerosis database |
RCV000043096 | SCV000066895 | not provided | Tuberous sclerosis syndrome | no assertion provided | curation |